Affinage

SMC6

Structural maintenance of chromosomes protein 6 · UniProt Q96SB8

Length
1091 aa
Mass
126.3 kDa
Annotated
2026-06-10
34 papers in source corpus 26 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMC6 is a core ATPase subunit of the conserved SMC5/6 complex that governs the recombinational repair and segregation of damaged and repetitive chromosomes (PMID:12966087, PMID:16892052). Together with SMC5 it forms the structural heterodimer of a holocomplex that incorporates the essential non-SMC subunits NSE1, NSE2, NSE3, and the NSE4 kleisin bridging the two SMC head domains, plus the NSE5/NSE6 heterodimer that contacts the SMC hinges (PMID:12966087, PMID:15331764, PMID:17005570, PMID:19141609). SMC6 itself is a strong, nucleotide-modulated DNA-binding protein with two independent DNA-binding domains — one in the hinge/coiled-coil region and one in the ATPase head — that prefer single-stranded DNA as monomers but gain double-stranded DNA affinity upon heterodimerization with SMC5 (PMID:21293191, PMID:22086171, PMID:25984708). The complex is recruited de novo to double-strand breaks and is essential for homologous recombination between sister chromatids while suppressing non-sister recombination and gross chromosomal rearrangements, particularly at repetitive loci such as rDNA, telomeres, and centromeres where it prevents accumulation of aberrant Holliday-junction intermediates (PMID:15793567, PMID:16892052, PMID:18585101, PMID:23284708). At collapsed replication forks SMC5/6 is tethered through an NSE5/6–Brc1–γ-H2A interaction that licenses its chromatin association and intrinsic SUMO ligase activity (PMID:30348841), and in human cells it is recruited to transcription–replication conflicts where it nucleates a BTRR–FANCM–FANCD2 resolution axis (PMID:41533569). SMC6 function ensures faithful chromosome segregation by enabling Separase-independent cohesin removal after DNA damage (PMID:19528228) and is required during meiosis to remove chromosome linkages (PMID:21731634, PMID:22855558). SMC6 is essential in mice, with ATPase-domain integrity required to limit damage-induced sister chromatid exchange and oxidative damage (PMID:23518413). The SMC6 subunit is directly targeted by the hepatitis B virus protein HBx, which engages a conserved 'Leucine Key' (LRCKL) motif on SMC6 to neutralize its restriction of viral episomal DNA.

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2003 High

    Established the core subunit composition of the SMC5/6 complex, defining SMC6 as part of a multi-subunit machine rather than a standalone factor and placing it in a Rhp51-dependent DNA repair pathway.

    Evidence Affinity purification/mass spectrometry, co-IP, and genetic epistasis in fission yeast

    PMID:12966087

    Open questions at the time
    • Stoichiometry and architecture of subunit contacts not yet resolved
    • Biochemical activity of the complex undefined
  2. 2004 Medium

    Identified NSE3 as an additional essential non-SMC subunit and showed SMC5/6 is required to sustain checkpoint-coupled repair — cells initiate Chk1 but enter lethal mitosis — distinguishing a repair/maintenance role from checkpoint initiation.

    Evidence Biochemical purification, checkpoint kinase phosphorylation assays, and live-cell phenotyping in fission yeast

    PMID:14701739 PMID:15331764 PMID:15485909

    Open questions at the time
    • Molecular mechanism by which the complex maintains arrest not defined
    • Direct DNA substrate not identified
  3. 2004 Medium

    Placed SMC6 directly in the Rad52/Rad51-dependent recombination pathway by showing it is required for MMS-induced sister chromatid and interchromosomal recombination.

    Evidence Temperature-sensitive smc6 mutants with epistasis to rad52 and recombination assays in budding yeast

    PMID:15010319

    Open questions at the time
    • Whether SMC5/6 acts before or after strand invasion unresolved
    • No biochemical reconstitution of its recombination role
  4. 2005 High

    Localized SMC5/6 to rDNA and telomeres and demonstrated it prevents accumulation of Holliday junctions at repetitive loci, explaining its role in segregating repetitive chromosomal regions.

    Evidence ChIP, 2D-gel Holliday junction detection, and genetic epistasis in conditional mutants

    PMID:15793567

    Open questions at the time
    • Mechanism by which junctions are prevented vs resolved not separated
    • Direct enzymatic activity on junctions not shown
  5. 2006 High

    Resolved the internal architecture of the complex, identifying NSE4 as the kleisin bridging SMC5 and SMC6 heads, and defining NSE5/6 as a distinct hinge-associated subcomplex required for replication fork stability.

    Evidence In vitro binding with recombinant proteins, yeast two-hybrid, domain mutagenesis, and genetic epistasis

    PMID:16478984 PMID:16892052 PMID:17005570

    Open questions at the time
    • How head-bridging kleisin couples to ATPase cycle unknown
    • Functional consequence of hinge-head geometry on DNA handling unclear
  6. 2007 High

    Linked SMC5/6 to SUMO-dependent spatial control of recombination by showing it excludes Rad52 foci from the nucleolus to prevent rDNA hyperrecombination, and connected NSE1 and the Mms21 SUMO ligase to Rad52-dependent post-replication repair.

    Evidence Live fluorescence microscopy, SUMO modification assays, and allele-specific genetic analysis

    PMID:17643116 PMID:17923688

    Open questions at the time
    • SUMO substrates driving exclusion not fully enumerated
    • Mechanism connecting NSE1 RING to repair undefined
  7. 2008 Medium

    Clarified that the NSE1 RING-like domain supports holocomplex integrity and damage-induced focus recruitment rather than acting as a detectable ubiquitin ligase, refining the functional assignment of complex subunits.

    Evidence In vitro ubiquitin ligase assays (negative), co-IP, in vivo focus formation, and mutagenesis; plus GCR assays showing BIR-dependent translocation suppression

    PMID:18585101 PMID:18667531

    Open questions at the time
    • Whether NSE1 has E3 activity in a different context unresolved
    • Substrate of any associated ligase not identified here
  8. 2009 High

    Mapped the spatial organization of all subcomplexes onto SMC5/6 (NSE5/6 at hinges, NSE1-3-4 at SMC5 head, NSE2 at middle coiled-coil) and revealed that mitotic lethality of smc6 mutants arises from failed Separase-independent cohesin removal.

    Evidence Yeast two-hybrid and in vitro binding for architecture; Separase overexpression rescue and cohesin persistence assays for segregation

    PMID:19141609 PMID:19528228

    Open questions at the time
    • Molecular mechanism linking SMC5/6 to cohesin removal undefined
    • How architecture supports cohesin function not established
  9. 2011 Medium

    Defined the biochemical DNA-binding behaviour of SMC6 and SMC5, showing each is a strong, nucleotide-modulated, ssDNA-preferring binder as a monomer, consistent with engaging replication/repair intermediates.

    Evidence In vitro EMSA DNA-binding assays with purified recombinant SMC5 and SMC6 and ATPase mutagenesis

    PMID:21293191 PMID:22086171

    Open questions at the time
    • Physiological DNA substrate not confirmed in vivo
    • Coupling of binding to ATPase cycle not resolved
  10. 2011 Medium

    Extended SMC5/6 function into meiosis, showing it removes chromosome linkages including Spo11-independent ones to permit segregation, and localizes to specific prophase chromosome regions.

    Evidence Immunofluorescence localization, spo11 epistasis, and chromosome segregation assays

    PMID:21731634

    Open questions at the time
    • Nature of the removed linkages unclear
    • Mechanism of region-specific localization unknown
  11. 2012 Medium

    Showed SMC5/6 regulates recombination at centromeres and that its Mms21 SUMO ligase sumoylates kinetochore proteins, and established that NSE5/6 promotes meiotic resolution of joint molecules via Mus81-Eme1.

    Evidence 2D gels for recombination intermediates, Rad52 foci imaging, SUMO assays, Southern blotting for joint molecules, RusA rescue, and epistasis

    PMID:22855558 PMID:23284708

    Open questions at the time
    • Direct kinetochore SUMO targets not fully validated
    • How NSE5/6 stimulates Mus81-Eme1 mechanistically unknown
  12. 2013 High

    Established SMC6 as essential in a mammal and tied ATPase integrity to suppression of sister chromatid exchange and oxidative damage, while documenting conservation of complex structure and HR function across Drosophila and mouse spermatogenesis.

    Evidence Mouse knockout, ATPase S994A knockin, sister chromatid exchange assays, immunofluorescence in testis, Drosophila genotoxin sensitivity and co-IP

    PMID:23518413 PMID:23555814 PMID:23907463

    Open questions at the time
    • Embryonic-lethal step in knockout not defined
    • Role of pericentromeric SMC6 localization in meiotic commitment unclear
  13. 2015 Medium

    Resolved the DNA-binding module organization, demonstrating two independent DBDs per SMC subunit (hinge/coiled-coil and ATPase head) and that heterodimerization increases dsDNA affinity, providing a structural basis for substrate engagement.

    Evidence In vitro EMSA with purified recombinant domain fragments

    PMID:25984708

    Open questions at the time
    • In vivo contribution of each DBD not dissected
    • How DNA binding is coordinated with ATP hydrolysis unknown
  14. 2019 High

    Defined the recruitment logic at collapsed replication forks: Brc1 bridges NSE5/6 and γ-H2A to tether SMC5/6 and activate its intrinsic SUMO ligase, explaining how the complex is targeted to replicative lesions.

    Evidence Co-IP, SUMO ligase activity assays, focus-formation imaging, and genetic epistasis in fission yeast

    PMID:30348841

    Open questions at the time
    • Human counterpart of this tether not addressed here
    • SUMO ligase substrates at forks not enumerated
  15. 2026 High

    Placed human SMC5/6 at the head of a transcription-replication conflict resolution axis, showing it recruits the BTRR complex (resolving via TOP3A catalysis) which then recruits FANCM to activate FANCD2.

    Evidence Synthetic lethality screen, ChIP/proximity ligation, TOP3A catalytic-mutant epistasis, and co-IP in human cells

    PMID:41533569

    Open questions at the time
    • How SMC5/6 senses supercoiling buildup not defined
    • Direct SMC6–BTRR contacts not mapped structurally
  16. 2025 Medium

    Defined the human regulatory subcomplex and viral antagonism interface: SIMC1-SLF2 (the Nse5/6 counterpart) is required for SMC5/6-mediated silencing of extrachromosomal DNA, and HBx engages a conserved SMC6 'Leucine Key' motif to counteract this restriction.

    Evidence Cryo-EM of the HBx-CRL4-SMC5/6 complex (preprint), reconstitution, reporter silencing assays, co-IP, and HBV replication assays

    Open questions at the time
    • Both reports are single-lab preprints awaiting peer review
    • Mechanism by which SIMC1-SLF2–SMC6 contact drives transcriptional silencing not defined
    • How SUMO pathway dependence connects to silencing unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the SMC6 ATPase cycle, its two DNA-binding domains, and SUMO ligase activation are mechanically coupled to discriminate and resolve recombination intermediates at distinct genomic loci remains unresolved.
  • No integrated structure-function model linking ATP hydrolysis to DNA loop/junction handling
  • Direct enzymatic activity of the complex on Holliday junctions not demonstrated
  • Full SUMO substrate landscape across loci undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0005198 structural molecule activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005730 nucleolus 2
Pathway
R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2
Partners
HBXNSE1NSE2NSE3NSE4NSE5NSE6SMC5
Complex memberships
NSE1-NSE3-NSE4 subcomplexNSE5/NSE6 (SIMC1-SLF2) subcomplexSMC5/6 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 SMC6 forms a high-molecular-mass complex with SMC5 and the non-SMC subunit NSE1 (identified by mass spectrometry after purification of fission yeast Smc5), establishing the core composition of the Smc5-6 complex required for DNA repair and proliferation. Affinity purification and mass spectrometry; co-immunoprecipitation; genetic epistasis with Rhp51 The Journal of biological chemistry High 12966087
2003 NSE1 and NSE2 are essential non-SMC subunits of the fission yeast Smc5-6 complex that interact with Smc5 in vivo; loss of Nse1 or Nse2 produces phenotypes identical to Smc5-6 inactivation, and epistasis places them in the same homologous-recombination DSB repair pathway as Rhp51. Affinity purification/mass spectrometry, co-IP, genetic epistasis The Journal of biological chemistry High 12966087
2004 NSE3 is an additional essential non-SMC subunit of the fission yeast Smc5-6 complex; it is required for mitotic chromosome segregation, resistance to genotoxic agents, and meiotic recombination-based DNA repair in a pathway epistatic to Rhp51. Biochemical purification, genetic epistasis, co-immunoprecipitation Molecular biology of the cell High 15331764
2004 The Smc5/6 complex is required for coordinated DNA damage response: fission yeast cells lacking functional Smc6 initiate a normal Chk1 checkpoint but then enter lethal mitosis, indicating Smc5/6 is needed to maintain checkpoint arrest through ongoing DNA repair rather than for checkpoint initiation. Genetic loss-of-function (smc6 and nse1 mutants), checkpoint kinase phosphorylation assays, live-cell phenotyping Molecular and cellular biology Medium 14701739
2004 Rad62 physically associates with the Smc5-6 complex and is required for recombinational repair of DSBs and recovery from stalled replication; its DNA repair role is epistatic with rhp51 and genetically interacts with rad60 and smc6. Co-immunoprecipitation, genetic epistasis, sensitivity assays Molecular and cellular biology Medium 15485909
2004 SMC6 is required for MMS-induced sister chromatid recombination and interchromosomal recombination in budding yeast; smc6-56 rad52 double mutants show MMS sensitivity similar to rad52 alone, placing Smc6 in the Rad52-dependent recombination pathway. Temperature-sensitive smc6 mutants, genetic epistasis with rad52, recombination assays DNA repair Medium 15010319
2005 Smc5 and Smc6 are enriched at rDNA and telomeres; conditional smc5-6 and smc6-9 mutants show impaired segregation of repetitive chromosomal regions, accumulation of Holliday junctions at rDNA, and RAD9-dependent Rad53 activation; deletion of RAD52 partially suppresses temperature sensitivity, indicating the complex prevents sister chromatid junctions at repetitive loci. ChIP, 2D gel electrophoresis (Holliday junction detection), genetic epistasis, conditional mutants Nature cell biology High 15793567
2006 NSE1 and NSE2 (with NSE3-NSE4) form a subcomplex within the Smc5-6 holocomplex; NSE4 is identified as the kleisin component that bridges the Smc5 and Smc6 head domains, with its C-terminal region interacting with the Smc5 head and a predicted winged-helix motif required for this interaction. Co-immunoprecipitation, yeast two-hybrid, in vitro binding with purified recombinant proteins, domain mutagenesis The Journal of biological chemistry High 17005570
2006 Nse5 and Nse6 form a distinct heterodimeric subcomplex within the Smc5-6 holocomplex; Nse5/6 mutants display high spontaneous DNA damage and are required for tolerance of UV lesions and stabilization/processing of stalled replication forks; their UV sensitivity is suppressed by deletion of Rad51 homolog Rhp51, and viability requires Mus81 and Rqh1, implicating Nse5/6 in suppressing aberrant recombination at replication forks. Genetic epistasis, sensitivity assays, RusA rescue experiment Molecular and cellular biology Medium 16478984
2006 The Smc5-Smc6 complex is recruited de novo to DSBs and is essential for repair by homologous recombination between sister chromatids (SCR), and suppresses gross chromosomal rearrangements by preventing non-sister recombination events. Chromatin immunoprecipitation (ChIP) at induced DSBs, genetic epistasis, GCR assays Nature cell biology High 16892052
2007 Smc5-Smc6 and Mre11 complexes mediate the nucleolar exclusion of Rad52 recombination foci at rDNA DSBs; this exclusion depends on SUMO modification of Rad52. Failure of this pathway leads to Rad52 foci within the nucleolus, rDNA hyperrecombination, and excision of extrachromosomal rDNA circles. Live fluorescence microscopy, SUMO modification assays, genetic epistasis Nature cell biology High 17643116
2007 Nse1, a subunit of the Smc5-Smc6 complex, is required for Rad52-dependent post-replication repair (PRR) of UV-damaged DNA; genetic analysis implicates both the Nse1 ubiquitin-ligase-like activity and the Mms21 SUMO-ligase activity of the complex in this Rad52-dependent repair mode. Genetic epistasis, UV sensitivity assays, allele-specific mutant analysis Molecular and cellular biology Medium 17923688
2008 The Nse1 RING-like domain supports Smc5-Smc6 holocomplex integrity: it is required for normal Nse1-Nse3-Nse4 trimer formation in vitro and for damage-induced recruitment of Nse4 and Smc5 to subnuclear foci in vivo. No ubiquitin E3 ligase activity was detected for full-length or isolated Nse1 RING domain in vitro. In vitro ubiquitin ligase assay, co-IP, in vivo focus formation (immunofluorescence), mutagenesis Molecular biology of the cell Medium 18667531
2008 The smc6-9 mutation increases translocation-class gross chromosomal rearrangements (GCRs) in a manner dependent on break-induced replication (BIR) and independent of NHEJ; translocations cluster near repetitive sequences, showing that Smc5-Smc6 suppresses GCR formation by reducing DNA damage at repetitive loci. GCR assay, genetic epistasis (BIR and NHEJ mutants), genome sequencing of rearrangements DNA repair Medium 18585101
2009 The Nse5-Nse6 heterodimer interacts with the hinge regions of both Smc5 and Smc6, while the Nse1-Nse3-Nse4 subcomplex binds to the head and adjacent coiled-coil of Smc5, and Nse2 binds the middle coiled-coil of Smc5; these three entities occupy distinct sites defining the Smc5/6 complex architecture. Yeast two-hybrid, in vitro binding with purified recombinant proteins The Journal of biological chemistry High 19141609
2009 In smc6 mutants after DNA damage, chromosome arm segregation fails due to aberrant persistence of cohesin that is normally removed by the Separase-independent pathway; overexpression of Separase bypasses this defect and restores viability, identifying defective cohesin removal as a major determinant of mitotic lethality in Smc5-Smc6 mutants. Genetic epistasis, cohesin persistence assays, Separase overexpression rescue Molecular and cellular biology High 19528228
2011 Smc5 binds strongly and specifically to single-stranded DNA (ssDNA) as a monomer independently of Smc6; this binding is regulated by ATP and is observed with ssDNA of ~60 nt or longer, consistent with substrates generated during DNA replication and repair. In vitro DNA-binding assay with purified recombinant Smc5, ATPase mutagenesis, EMSA Cell cycle (Georgetown, Tex.) Medium 21293191
2011 Smc6 is a strong DNA-binding protein with preference for single-stranded DNA; it binds DNA independently of other Smc5-6 complex components and its activity is modulated by nucleotides; the minimal ssDNA size for tight association is ~60 nucleotides. In vitro DNA-binding assay with purified recombinant Smc6, EMSA Biochemical and biophysical research communications Medium 22086171
2011 In meiosis, the Smc5-Smc6 complex is required for removing chromosome linkages (including those independent of Spo11-induced recombination) to allow proper chromosome segregation; the complex localizes to specific chromosome regions during meiotic prophase I. Immunofluorescence localization, genetic (spo11 epistasis), chromosome segregation assays PloS one Medium 21731634
2012 Smc6 mutation leads to accumulation of recombination intermediates at centromeres (assayed by 2D gel) and increased centromere-associated Rad52 foci; a rad52 mutation suppressing centromeric Rad52 foci also suppresses nocodazole sensitivity of smc6 mutants, showing that Smc5-Smc6 regulates recombination at centromeric loci. The SUMO ligase subunit of Smc5-Smc6 (Mms21) also promotes sumoylation of kinetochore proteins and affects mitotic spindles. 2D gel electrophoresis, fluorescence microscopy (Rad52 foci co-localization), SUMO modification assays, genetic epistasis PloS one Medium 23284708
2012 Nse5-Nse6 of the Smc5-Smc6 complex is required for meiotic resolution of Holliday junction-like recombination intermediates (DNA joint molecules) via promotion of Mus81-Eme1 endonuclease activity; RusA bacterial resolvase partially rescues nse6Δ meiotic defects, and elimination of Rec12 (Spo11) nearly completely rescues defects, placing Nse5-Nse6 after DSB formation in the meiotic recombination pathway. Southern blotting for DNA joint molecules, RusA rescue, genetic epistasis (rec12Δ, mus81Δ) Nucleic acids research High 22855558
2013 SMC6 is an essential gene in mice (complete knockout causes early embryonic lethality); a hypomorphic ATPase domain mutation (S994A) results in viable mice with sensitivity to induction of sister chromatid exchanges by UV and mitomycin C, and accumulation of oxidative damage, but not sensitivity to killing by DNA-damaging agents. Gene knockout, ATPase point mutant knockin, sister chromatid exchange assay, embryonic fibroblast sensitivity assays DNA repair High 23518413
2013 During mouse spermatogenesis, Smc6 localizes to pericentromeric heterochromatin domains specifically when differentiating spermatogonia commit irreversibly toward meiosis; Smc6-negative meiotic cells fail to complete the first meiotic division; DNA repair/recombination sites (γH2AX, Rad51) do not co-localize with the Smc6-positive pericentromeric domains. Immunofluorescence/localization in testis sections, co-localization analysis, meiotic staging Cell death & disease Medium 23907463
2013 In Drosophila, SMC6 (CG5524) mutants are hypersensitive to genotoxic agents (ionizing radiation, camptothecin, hydroxyurea, MMS); MAGE physically interacts with Drosophila Nse homologs, indicating conservation of the SMC5/6 complex structure; caffeine-induced apoptosis in smc6 mutants is suppressed by Rad51 depletion, placing SMC6 in a homologous recombination repair pathway. Genetic screen, genotoxin sensitivity assays, co-immunoprecipitation, genetic epistasis (Rad51 depletion) PloS one Medium 23555814
2015 The Smc5-Smc6 heterodimer contains two independent DNA-binding domains (DBDs) in each SMC subunit: one in the hinge/coiled-coil region and one in the ATPase head domain; heterodimerization of full-length proteins specifically increases affinity for double-stranded DNA substrates compared to monomers. In vitro DNA-binding assays with purified recombinant domain fragments, EMSA Scientific reports Medium 25984708
2019 Brc1 (fission yeast) is required for the focal accumulation (foci formation) of the Smc5-Smc6 complex during replication stress and for activation of its intrinsic SUMO ligase activity at collapsed replication forks; the Nse5-Nse6 heterodimer is required for chromatin association and SUMO ligase activity of Smc5-Smc6; Brc1 interacts physically with Nse5-Nse6 and with γ-H2A, thereby tethering Smc5-Smc6 at replicative DNA lesions. Co-immunoprecipitation, SUMO ligase activity assay, immunofluorescence focus formation, genetic epistasis Molecular and cellular biology High 30348841
2026 The human SMC5/6 complex is recruited to transcription-replication conflicts (TRCs) in response to DNA supercoiling buildup in SETX-deficient cells; once recruited, SMC5/6 facilitates recruitment of the BLM/TOP3A/RMI1/RMI2 (BTRR) complex, which resolves TRCs in a TOP3A catalytic-activity-dependent manner; BTRR in turn recruits FANCM to activate the FANCD2 pathway, defining the SMC5/6-BTRR-FANCM-FANCD2 axis. Synthetic lethality screen, ChIP/proximity ligation for recruitment, epistasis with TOP3A catalytic mutant, co-immunoprecipitation Nucleic acids research High 41533569
2025 Cryo-EM structure of the human HBx-CRL4-SMC5/6 complex at 3.1 Å resolution reveals that HBx adopts a zinc-stabilized Y-shaped architecture and directly contacts the SMC6 subunit via a conserved 'Leucine Key' motif (LRCKL) on SMC6 that fits into a helix-turn-helix (HTH) pocket on HBx; disrupting this interface with Tranilast suppresses HBV replication. Cryo-electron microscopy (3.1 Å), reconstitution of ten-subunit complex, molecular docking, biochemical validation, HBV replication assay bioRxivpreprint High
2025 SMC5/6-mediated repression of extrachromosomal circular/plasmid DNA transcription depends exclusively on the SIMC1-SLF2 subcomplex (the human counterpart of yeast Nse5/6) and requires a conserved SIMC1-SLF2–SMC6 interaction; SLF1/2 is dispensable for plasmid silencing; plasmid silencing requires the SUMO pathway but not PML nuclear bodies. Reporter-based transcriptional silencing assay, co-immunoprecipitation, genetic knockdown/knockout bioRxivpreprint Medium

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nature cell biology 331 17643116
2006 Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nature cell biology 161 16892052
2005 SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nature cell biology 160 15793567
2006 The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Molecular and cellular biology 123 16478984
2003 Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. The Journal of biological chemistry 102 12966087
2004 Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis. Molecular biology of the cell 98 15331764
2009 The unnamed complex: what do we know about Smc5-Smc6? Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 94 19308705
2006 The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits. The Journal of biological chemistry 91 17005570
2002 Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. The Journal of biological chemistry 89 11927594
2004 Coordination of DNA damage responses via the Smc5/Smc6 complex. Molecular and cellular biology 83 14701739
2009 Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. The Journal of biological chemistry 78 19141609
2004 Rad62 protein functionally and physically associates with the smc5/smc6 protein complex and is required for chromosome integrity and recombination repair in fission yeast. Molecular and cellular biology 59 15485909
2008 Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Molecular biology of the cell 54 18667531
2004 SMC6 is required for MMS-induced interchromosomal and sister chromatid recombinations in Saccharomyces cerevisiae. DNA repair 43 15010319
2009 Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Molecular and cellular biology 41 19528228
2012 Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6 holocomplex. Nucleic acids research 37 22855558
2011 Dynamic and selective DNA-binding activity of Smc5, a core component of the Smc5-Smc6 complex. Cell cycle (Georgetown, Tex.) 35 21293191
2013 Role for rodent Smc6 in pericentromeric heterochromatin domains during spermatogonial differentiation and meiosis. Cell death & disease 34 23907463
2012 The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth. PloS one 31 23284708
2008 Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA repair 28 18585101
2007 Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Molecular and cellular biology 26 17923688
2011 The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis. PloS one 24 21731634
2013 SMC6 is an essential gene in mice, but a hypomorphic mutant in the ATPase domain has a mild phenotype with a range of subtle abnormalities. DNA repair 22 23518413
2019 Brc1 Promotes the Focal Accumulation and SUMO Ligase Activity of Smc5-Smc6 during Replication Stress. Molecular and cellular biology 21 30348841
2011 DNA-binding properties of Smc6, a core component of the Smc5-6 DNA repair complex. Biochemical and biophysical research communications 19 22086171
2005 Smc5-Smc6 complex preserves nucleolar integrity in S. cerevisiae. Cell cycle (Georgetown, Tex.) 19 15917663
2013 The Smc5/Smc6/MAGE complex confers resistance to caffeine and genotoxic stress in Drosophila melanogaster. PloS one 17 23555814
2015 The Smc5-Smc6 heterodimer associates with DNA through several independent binding domains. Scientific reports 16 25984708
2019 Recruitment, loading, and activation of the Smc5-Smc6 SUMO ligase. Current genetics 14 30600397
2013 DNA damage checkpoint and recombinational repair differentially affect the replication stress tolerance of Smc6 mutants. Molecular biology of the cell 13 23783034
2015 Nse1 and Nse4, subunits of the Smc5-Smc6 complex, are involved in Dictyostelium development upon starvation. Development, growth & differentiation 5 26036668
2026 The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts. Nucleic acids research 1 41533569
2025 The Phenotype of Physcomitrium patens SMC6 Mutant with Interrupted Hinge Interactions. Genes 0 41010035
2025 SMC6 expression & outcome of breast cancer. The Indian journal of medical research 0 41520270

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